Role of MDA-7/IL-24 a Multifunction Protein in Human Diseases

Abstract

Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24). Discovered in the early 1990s, MDA-7/IL-24 has proven to be a potent, near ubiquitous cancer suppressor gene capable of inducing cancer cell death through apoptosis and toxic autophagy in cancer cells in vitro and in preclinical animal models in vivo. In addition, MDA-7/IL-24 embodied profound anticancer activity in a Phase I/II clinical trial following direct injection with an adenovirus (Ad.mda-7; INGN-241) in tumors in patients with advanced cancers. In multiple independent studies, MDA-7/IL-24 has been implicated in many pathological states involving inflammation and may play a role in inflammatory bowel disease, psoriasis, cardiovascular disease, rheumatoid arthritis, tuberculosis, and viral infection. This review provides an up-to-date review on the multifunctional gene mda-7/IL-24, which may hold potential for the therapy of not only cancer, but also other pathological states.

CYTL1 inhibits tumor metastasis with decreasing STAT3 phosphorylation

“…Many cytokines, such as IL-24 and IL-37, exert tumorsuppressing effects and related clinical trials of tumor treatment have been conducted. 15,18 In our article, we demonstrated that both recombinant CYTL1 and overexpression of CYTL1 could inhibit the migration of multiple types of tumor cells. It is possible that the tumorsuppressing cytokine CYTL1 might be used in tumor treatment, such as lung cancer and breast cancer.…”

“…For instance, IL-24 has been proven to suppress multiple signaling pathways in various human cancer cells, such as melanoma, cervical cancer, lung cancer and prostate cancer, 13 and this suppressive effect leads to tumor cell death and the inhibition of tumor angiogenesis and metastasis. 14,15 Because recombinant IL-24 shows selective cytotoxicity against cancer cells, clinical trials have investigated the use of IL-24 for the treatment of solid tumors. 16,17 Another example is IL-37, whose intracellular mature form markedly inhibits the migration of multiple types of tumor cells by inhibiting Rac1 activation.…”

Interleukin-24 Regulates T Cell Activity in Patients With Colorectal Adenocarcinoma

“…Low concentration of IL-24 promotes inflammatory cytokine expression, leading to the proinflammatory response. In contrast, high concentration of IL-24 strongly induces apoptosis of cancer cells (12,14). IL-24 expression was remarkably correlated with histological differentiation, but inversely correlated with the degree of lymph node involvement in rectal cancer (15), which played an important anti-tumor role for colon cancer therapy (16,17) and even reversed multidrug resistance to chemotherapy in human colorectal cancer cells (18).…”

Increased expression of IL‐24 in chronic spontaneous urticaria

“…6 IL-24 is also implicated in autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis. 7 In light of the identification of IL24-directed IgE in CSU, we wondered whether local IL-24 is produced during the urticarial reaction.…”